Extended

Project
Qualificati
on
To what extent
does epigenetics
threaten the
credibility of
Darwins theory of
evolution?
Alex Nagle

Contents
Introduction - What is Evolution?
Page 2

Charles Darwin and Natural Selection

Page 2

Epigenetics
Page 4

Mechanisms of Epigenetics
Page 5

Is Darwins Theory at Risk?

Page 7

Conclusion
Page 8

Bibliography
Page 9

Fig. 1. Charles Darwin

Introduction - What is Evolution?

The word evolution originates from evolvere, the Latin word meaning to unfold or
unroll [1]. Commonly, evolution is applied to mean change, in a broader sense of the
word; more specifically, a change in which there is inheritance of previous characteristics
across the formation of each new generation of an entity. Therefore, with a non-biological
understanding, evolution can be pertained to descent with modification, and often with
diversification [1].
However, taken from a biological perspective, evolution involves the transference
of genetic information of an organism (its genome) to the consequent generation. This
results in the acquisition of similar characteristics between parent and offspring. Most
areas of biology and, in fact, science in general are often rarely disputed due to the
myriad of evidence built up by scientists that make it absurd to say anything otherwise.
Yet evolution is one of the few areas of science that is frequently contested to such an
extent that it is often debated as to which theory should be taught in schools. This is not
due to lack of evidence necessarily, but because evolution is such a process that, by its
nature, only shows itself truly over a span of many generations, far longer than a single
human spends on Earth during its lifetime. As a result, the process cannot be viewed
directly, introducing the opportunity for many opinions to be made, without the ability to
disprove them indefinitely.
Such hypotheses and theories include Darwinism (or Neo-Darwinism), Lamarckism
and Creationism. For many centuries, Creationism stood tall as the only conceivable
mechanism that could have resulted in complex life, the belief that the universe and
living organisms originate from specific acts of divine creation [2]. Later, however, others
began to question the credibility of this theory. Jean Baptiste Lamarck entered onto the
evolutionary stage in 1744. Lamarck managed the invertebrate collection at the Natural
History Museum in Paris, and noticed similarities between current species and fossils,
revealing the physical links between them and the possible pathway that one species
may have taken to form a modern one. The French biologist published his theory of
evolution in 1809, including the idea of the inheritance of acquired characteristics,
whereby the attributes that an organism develops over its lifetime may be heritable [3].
However, there was little evidence to support Lamarcks theory, and the majority of
people at the time were still confident in the idea of an omnipotent God who created all

living things. Whilst most scientists are currently agreed that characteristics that one
acquires over the course of their life cannot be passed onto the next generation, Lamarck
was one of the first to acknowledge the gradual development of species over time. This
was an idea that would be consolidated and refined by Charles Darwin later on in the
same century.

Charles Darwin and Natural Selection

Darwin was born in 1809, the same year that Lamarck published his theory on the
inheritance of acquired characteristics. After enrolling at Christ Church at Cambridge
University, Darwin decided to take a trip around the world by sea, a journey that would
prompt a huge leap in the understanding of evolution. The discoveries made on Voyage
of the Beagle (see Fig. 2.) in December 1831 formed the basis of evidence that Darwin
recalled to construct his own evolutionary theory: natural selection.

Fig. 2. The HMS Beagle in the Straits of

Magellan

When travelling to the Galapagos Islands, approximately 900km west of Ecuador,

Darwin noticed how the fauna on the islands, whilst being particular to this small region
of the world, seemed to share certain characteristics with species on mainland South
America. He concluded that the Islands were inhabited by species that had strayed from
the mainland and diversified as a result of the separation [3]. Several observations and
deductions were made over the course of the trip that helped Darwin consolidate his
theory and write the world renowned The Origin of Species. These would open the minds
of previously stubborn creationists to the possibilities of a natural process, such as the
one Darwin presents. The following are the observations and deductions made when
Darwin visited the Galapagos Islands.

Observations

Deductions

Species over-reproduce
Population sizes remain
constant
Organisms within a species
vary
This variation can be heritable

There is a struggle for

existence
Organisms with the most
appropriate characteristics for
the environment are most likely
to survive and reproduce
These characteristics can be
passed onto the next
generation [4]

Thus, the theory of natural selection was born in 1859 with the publication of The
Origin of Species which gave Darwin the ability to put his discoveries on display to the
public. Whilst this unprecedented concept first faced much cynicism, its popularity soon

slowly gained speed and formed a momentum so great that it broke down the walls of
almost any opposing theory.
Natural selection relies on genetic variation between organisms of a species that
means that some are more suited to thrive in their environment than others. For
example, some giraffes have long necks and some have shorter ones. If something
caused the low-lying shrubs to die out, the giraffes with the shorter necks will not be able
to reach food as easily, and will subsequently die out as a result (see Fig. 3.). The giraffes
with the longer necks are more suited to their environment, and therefore are more likely
to survive and reproduce, passing their genetic information onto the next generation,
which will also have long necks [5]. It is a heritable trait. The absence of the low-lying
shrubs, in this case, is known as a selection pressure because it favours organisms of a
species with one characteristic over another (giraffes with long necks over giraffes with
short necks), bringing about a change in a populations range of variation.

Fig. 3. Natural Selection Giraffe

Necks

What remains to be answered is how some giraffes develop long necks whilst
others have shorter ones. This occurrence arises due to what scientists call mutations.
Lamarck suggested that giraffes stretched their necks to reach the higher leaves, and as
a result, their necks would become longer and this characteristic could be passed onto
the next generation [6]. However, Darwin tells us that mutations are behind this
development, permanent changes of the nucleotide sequence of the genome of an
organism, often caused by errors in the process of replication of genetic information [7].
Mutations are random, and therefore can be beneficial to an organism, or
contrastingly, detrimental. In the previous context of the giraffe, errors in the replication
of the genome (genetic material) of one giraffe resulted in a mutation that caused it to
have a longer neck. Because giraffes with longer necks are more suited to its
environment, it is more likely to survive and reproduce, and its offspring will, in turn,
inherit the genetic material that codes for it to have a long neck. On the other hand, the
giraffes with shorter necks cannot compete; they are less suited to thrive in their
environment, so less of them survive and pass on their genes, until a population is
reached where there are only giraffes with long necks.
An organisms genetic material, DNA (deoxyribonucleic acid) is comprised of four
nitrogenous bases: adenine, thymine, cytosine and guanine. If the order of these bases
within a polynucleotide chain is changed (a mutation), the complimentary RNA molecules
will also differ, resulting in a different protein being formed. Proteins are essential in
many metabolic and structural roles, and a change in the production of a certain
property can, therefore, potentially create large differences in the characteristics of an
organism. The diagram below (Fig. 4.) shows how Sickle Cell Anaemia may be inherited
from a mutation. Each base stands for a letter, A, T, C and G respectively.

Fig. 4. Mutations at the DNA Level

Epigenetics
A fairly recent arrival on the evolutionary radar is epigenetics. The prefix, epi, is
Greek for over, outside of or around, suggesting how gene expression has other causes
that escape the confines of cellular phenotypes being expressed solely through changes
in the order of nitrogenous base sequences within DNA [8]. Rather, epigenetics denotes
the idea that external or environmental factors have the ability to activate or deactivate
certain genes that bring about a change in an organism, independent of the DNA
sequencing of its genome. These characteristics can often be heritable. For that reason,
epigenetics not only contradicts Darwin, who denied this possibility, but instead
compliments Lamarck, who argued that characteristics acquired in an organisms lifetime
can be inherited.
Not even Neo-Darwinism, the modern synthesis of Darwinism which exists in
tandem with Mendelian genetics1 includes any idea that acquired characteristics can be
inherited by offspring. It is important to note, however, that epigenetics does not rule out
ideas of natural selection and gene mutation; it simply adds to this theory, albeit a rather
radical addition.
Despite epigenetics being coined approximately fifty years ago, only recently has
this area of biology been considered as something with the potential to revolutionise the
way in which inheritance is conceived. The future of epigenetics will reveal the
complexities of genetic regulation, cellular differentiation, embryology, aging, cancer,
and other diseases [9]. The emerging field has been stamped by many biologists as a
scientific revolution [10]

Mechanisms of Epigenetics
Unlike Darwins evolution, where dependable observations can only really be seen
over the course of many generations, epigenetics presents the opportunity for the
acquisition of characteristics to be viewed between just two generations. It proceeds
through two primary mechanisms: DNA methylation and histone modification. These are
both changes to the genome of the organism, yet do not have any effect on the
sequencing of the nitrogenous bases, hence being labelled epigenetic processes rather
than genetic processes.

1 In Darwins time, the presence of genetic material was not known. He worked more on
a macro level, simply observing the patterns of evolution. Gregor Mendel (1822-1844)
refined the idea through the discovery of alleles and the intricacies of the process. The
combination of Mendelian genetics with Darwins theory forms Neo-Darwinism.

DNA Methylation
One way in which gene expression is thought to be controlled is through DNA
methylation. This is where a methyl group consisting of one carbon atom and three
hydrogen atoms (CH3) combines with a nitrogenous base within the DNA double helix
(see Fig. 5.). However, this process is only applicable with adenine and cytosine. We have
known for some time that DNA methylation occurs frequently within our genetic material,
but it is only recently that scientists have begun to acknowledge its importance with
regards to gene expression. It is thought that the presence of a methyl group being
attached to a nitrogenous base can directly prevent transcription factors (proteins that
bind to specific DNA sequences to control transcription of the genetic material) from
binding to the gene promoter [11]. A gene promoter is a section of DNA that initiates
DNA transcription, where a complimentary RNA strand is produced and sent off to
produce a protein [12]. As a result, these sections of the DNA are effectively silenced,
meaning that the gene cannot be expressed. DNA methylation is also named tagging,
as it labels a gene to be, in essence, switched on or off.

Fig. 5. DNA Methylation

The process was first seen to possess the ability to control gene expression
through the discovery of its role in the formation of cancerous tumours. It is thought that
tumour suppressor genes that have been methylated, can lead to the formation of a
tumour. This is because the gene is rendered inactive by the presence of the methyl
groups inhibiting the transcription factors, and the gene is therefore not able to do its job
to suppress the formation of tumours. This is often caused by hypermethylation, the
increase in epigenetic methylation of adenine and cytosine [13].
So how exactly does this have consequences for evolution and the inheritance of
characteristics? It is thought that DNA methylation is heritable. In fact, not only is it
heritable, but that it can be controlled through the course of your life. For example, as
you age, there are noticeable changes of methylation within your genome. Some areas
are hypermethylated and some are hypomethylated, leading to some genes being
silenced and others being activated, respectively. Either way, scientists infer that this
change in methylation leads to greater susceptibility to certain diseases, such as
atherosclerosis. As you age, it is discovered that genes that suppress atherosclerosis are
hypomethylated (become more active) and genes that repress atherosclerosis are
hypermethylated (become more inactive) leading to a greater chance of having the
disease [14].
Furthermore, it is thought that lifestyle choices, such as diet can have an impact
on DNA methylation. People who are obese have DNA that is differently methylated from
those who are normal and healthy. This results in differences of gene expression that can
cause diseases like type 2 diabetes, a disease previously known to be linked with obesity,
but only recently has it been discovered exactly how. One experiment, carried out by a
group of eleven scientists in 2013, found that the new-born children of obese parents had
DNA that was similarly methylated, and therefore had similar gene expressions,
increasing the chance of the
child having diseases such as type 2 diabetes when they get older [15].

This idea is constantly being researched and is only in its primitive stages in
proving indefinitely that DNA methylated can, firstly, be controlled through external and
environmental factors and, secondly, be passed onto the next generation. Because
investigations into DNA methylation only began relatively recently, scientists find it hard
to say how many generations can be impacted by a single persons lifestyle choice.
However, educated inference deduces that the effects of epigenetic modifications can
last ten generations. Therefore, the process is not considered to be one that is
permanent over an infinite number of generations. At least, that is the current
assumption. There is no knowing how much the theory will develop over the next few
years given the current amount of research being undertaken.
If we apply this knowledge to Lamarcks giraffe theory, it can be argued that there
is some truth to it after all. As the giraffe stretches its neck and becomes longer, it is
possible, if we utilize the idea of DNA methylation, that certain genes will be turned on or
off as a result. This change can then be passed onto the next generation for the offspring
also to have a long neck. As already mentioned, this idea can only be conjectured at this
stage due to the undeveloped nature of the theory, and the, as yet, basic understanding
as to exactly which acquired characteristics are heritable. Despite this, this form of
epigenetics does pose a threat to the credibility of Darwins theory, due to patterns seen
in examples like obesity and aging, where methylation of the genetic material can have a
direct effect as to which genes are expressed and repressed.

Histone Modification
The second epigenetic process of controlling gene expression is histone
modification. Histones are proteins found in eukaryotic cells which regulate the structure
of chromatin within the nucleus. The DNA wraps itself around the histones, similarly to
wool around a spool (see Fig. 6.), and helps the genetic material to be condensed into
smaller structural units known as nucleosomes [16]. If this process did not occur, the
DNA would simply not fit as easily into the nucleus.

Fig. 6. Genomic Architecture

Furthermore, modifications to these histones have a potentially huge role in gene

expression. For example, acetylation, methylation and phosphorylation can take place on
the histones, modifying their structures slightly. The most common modifications are
those of methylation and acetylation to the lysine R groups at histone tails. Lysines have
a positive charge which is attracted to the negative charge of the DNA, increasing the
affinity that they have for each other. Acetylation of lysine on the histone tail removes
this positive charge, and therefore the affinity between the DNA and the histones,
leading to a much looser
structure of genetic material around the proteins. This, in turn, can cause the DNA to
become more open and allow transcriptional machines to have easier access to the
promoter regions. As a result, certain genes may be activated by this process. Other

modifications to histones can cause the DNA to wrap more tightly around them, reducing
a genes availability to transcription factors [17].
Lifestyle choice is also known to affect histone modification to some degree. It is
thought that bad choices in diet can cause, through acetylation and methylation of
various histones, various genes to be suppressed that protect against certain diseases
such
as
hypertriglyceridemia,
hypercholesterolemia,
hyperinsulinemia,
and
hyperleptinemia, increasing the chance of acquiring them [18].
Similarly to DNA methylation, this process affects gene expression without making
any changes to the sequence of the nitrogenous bases, which Darwin denied the
possibility of. However, also like DNA methylation, this form of epigenetics has only been
found to be very weakly transgenerational. In some cases, histone modifications are only
maintained over a few cell divisions, let alone from parent to offspring. This field of
biology is rapidly expanding and much research is being done to show exactly how
potent the mechanisms of epigenetics can be in evolution and, therefore, in disproving
some of Darwins theory. The idea suggests that characteristics passed onto the next
generation do not occur solely from random mutations, but that we can consciously
control those that we acquire and therefore pass down to our offspring an exciting idea
that no doubt has repercussions for almost every aspect of biology and, indeed, society.

Is Darwins Theory at Risk?

The evidence we have just encountered shows how epigenetic transgenerational
inheritance is possible in certain circumstances. Yet if we put this into the wider context
of evolution, will this relatively new field really have any potential to drastically change
the way in which we perceive the credibility of Neo-Darwinism? Currently, scientists
working in the area seem to have slightly different opinions on the future of epigenetics
and its possible impact on the biological world.
Elizabeth Pennisi in Science Magazine says that for some evolutionary biologists,
just hearing the term epigenetics raises hackles. They balk at suggestions that
something other than changes in DNA sequences has a role in evolution [19]. This
interesting quotation implies how Darwins ideologies have been considered as
irrefutable fact for so long, that the thought of another factor to evolution simply doesnt
add up. It is amazing how such a major development such as epigenetics has apparently
remained buried for so long and has only just emerged recently as a milestone for many
areas of biology. Oliver Rando, an epigenetics researcher at the University of
Massachusetts asks, Why hasnt this been obvious to all the brilliant researchers in the
past hundred years of genetics [10]? A legitimate question indeed. This is possibly why
some scientists are slightly sceptical of the idea and reserve their excitement before
some more substantial, water-tight evidence is released. This sentiment is backed by
Koen Verhoeven at the Netherlands Institute of Ecology in Wageningen, who says "a lot
more hard evidence is necessary before one can claim that epigenetics plays a very
important role in evolution" [19].
So a lot of biologists seem to keeping a very reserved and placid mindset towards
the future of epigenetics, not leaping to any conclusions. Yet amongst this hushed
atmosphere, one can only sense a unanimous aura of enthusiasm and excitement at the
possibilities. And indeed there are many scientists who do not hold back this feeling. Dr
Michael Skinner, a professor in the School of Biological Sciences at Washington State
University was one of the first people to produce a study that supported the idea of the
environment causing epigenetic changes in the DNA that could be inherited through the
gametes. In an interview, he said I think the future will actually be incorporating
environmental epigenetics into nearly every area of biology, from health to evolution,
and I think thats what we are going to see over the next decade or so [20]. Despite the
scepticism and lack of research, epigenetic transgenerational inheritance is a process
that has been proven by many renowned experts and its potential cannot simply be
ignored. Dr Skinner mentions that epigenetics doesnt just affect evolutionary biology,

but many other areas such as cellular differentiation, tissue development, environmental
induced disease aetiology, epigenetic transgenerational inheritance, and the general
systems biology of organisms [21]. In some of these fields, epigenetics has already
begun to take on a more active role and is being considered more seriously. It is possibly
just a matter of time before the same stage is reached in evolutionary biology.
Yet if all that is said about epigenetics is proven to be correct, and the anti-climax
that many people are expecting is flipped on its head by up and coming research, exactly
how detrimental will this to be to the credibility of Darwins theory of evolution? It is
important to remember that epigenetics does not disprove Darwins philosophy by any
stretch of the imagination it adds to it and refines it with an improved level of accuracy
and detail. The molecular biologist, Graham Templeton, says in an online article that
natural selection is still largely unchanged from Darwins original version, and is still the
overwhelmingly important force behind biological evolution [10]. All that Darwin said
would not be nullified as a result; it just happens that his findings do not tell the whole
story of evolution. I do not believe that this biological revolution, as some scientists call
it, will dethrone the 19th century scientist as the figure head of evolution. Neither will it
lift Jean Baptiste Lamarck to utmost praise, considering that Lamarck had no
understanding of epigenetics or,
indeed, genetics, as the presence of DNA was only found to exist years later. His
hypothesis was merely based on observations he made of current organisms, and it was
therefore most likely luck that helped him stumble upon the gold mine of epigenetics
that has just recently been unearthed.
The ferocious battle of late between epigenetics and Darwin has masked the fact
that there are other theories of evolution besides these. Since the arrival of epigenetics
and its fascinating potential, other concepts have emerged to take advantage of this new
debate. Dr Jeffrey P. Tomkins, who earned a masters degree in plant science from the
University of Idaho and who is also a research associate at the Institute for Creation
Research says, the predictions based on the Bible are aligning well with real
experimental science. He also states (August 2014) that the amazing cellular
machinery that reads, regulates, replicates, and modifies epigenetic states in the
genome is so incredibly sophisticated and complex that it can only be attributed to the
work of an Omnipotent Creator [22]. These quotations show how the increased intricacy
and ramification that epigenetics brings, favours the opinion of many that such
complexity could not have just occurred by chance, and that Creationism (not another
rendition of Neo-Darwinism) is the logical answer amongst the controversy. As a result,
the credibility of Darwins theory of evolution is weakened for many people, with this
added knowledge a more indirect consequence of the arrival of epigenetics. Yet despite
the above quotation, and the biological, academic background of Tomkins that somewhat
adds to the weight of his statement, it is clear that Creationism directly contradicts many
well supported concepts of biology that are steeped in evidence. For example, analysis of
fossils and molecular information (including epigenetics) of organisms past and present
clearly shows a gradual development of complex life from basic, unicellular beginnings,
something that Creationists strongly deny. Therefore, the presence of epigenetics may
have contrasting effects on Creationism and Neo-Darwinism as well as what Tomkins
suggests.

Conclusion
As can be seen, there is a wealth of opinions on the matter of evolution, still before
the rise of epigenetics, which has increased interest in the area by tenfold. Through
evidence such as DNA methylation and histone modification, the actual presence of
epigenetics as a biological force cannot be negated. We know that it is possible to alter
the genetic material of an organism (with modified gene expression and phenotypes as a
result) without varying the sequence of nitrogenous bases within the DNA molecule. It
has also been shown, through various scientific studies, that these alterations to the

genome can, in certain circumstances, be heritable, yet the potency of this

transgenerational inheritance is the quandary that faces biologists currently at the
forefront of their research. The outcome of this question will, I believe, define the extent
to which epigenetics will revolutionise biology and society in general.
If these epigenetic changes are deemed to be stable across many generations, it is
much more likely that Darwins theory will, at the very least, receive yet another
reformation which will this time be quite substantial. Few deny that epigenetics will make
a mark upon the biological world; the question that most scientists ask now is the scale
of its impact. In the last decade, we have already seen increased success with
treatments to cancer and a greatly heightened understanding of developmental biology.
The potential of epigenetics to do so much more, with vast quantities of research still to
be done, is an extremely exciting prospect, yet the only thing the world can currently do
is watch and wait and hold their breath.
In my opinion, I believe that the unassailable evidence, on a molecular level, that
epigenetics supplies, will no doubt have repercussions in almost every area in biology. Yet
at this present moment in time, it would be nave to say for certain that epigenetics will
greatly modify our understanding of evolution. As said previously, no matter what the
outcome, Darwins theory will not be disproved, rather refined. Natural selection is yet to
cast its vote as to which theory truly is the fittest to survive.

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